Vitamin D Deficiency and Its Association with Iron Deficiency in African Children.

Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.

Prevalence and predictors of vitamin D deficiency in young African children.

Background: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children.

Malaria is a cause of iron deficiency in African children.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria, as an instrumental variable in Mendelian randomization analyses.

Systemic iron reduction by venesection alters the gut microbiome in patients with haemochromatosis.

Background & Aims: Iron reduction by venesection has been the cornerstone of treatment for haemochromatosis for decades, and its reported health benefits are many. Repeated phlebotomy can lead to a compensatory increase in intestinal iron absorption, reducing intestinal iron availability. Given that most gut bacteria are highly dependent on iron for survival, we postulated that, by reducing gut iron levels, venesection could alter the gut microbiota.

Estimating the burden of iron deficiency among African children.

Background: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children.

Insights into pancreatic β cell energy metabolism using rodent β cell models.

Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile.

Blood biomarkers with Parkinson's disease clusters and prognosis: The oxford discovery cohort.

Background: Predicting prognosis in Parkinson's disease (PD) has important implications for individual prognostication and clinical trials design and targeting novel treatments. Blood biomarkers could help in this endeavor.

Methods: We identified 4 blood biomarkers that might predict prognosis: apolipoprotein A1, C-reactive protein, uric acid and vitamin D.

Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge.

Background: To accurately assess micronutrient status, it is necessary to characterize the effects of inflammation and the acute-phase response on nutrient biomarkers.

Objective: Within a norovirus human challenge study, we aimed to model the inflammatory response of C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) by infection status, model kinetics of micronutrient biomarkers by inflammation status, and evaluate associations between inflammation and micronutrient biomarkers from 0 to 35 d post-norovirus exposure.

Methods: Fifty-two healthy adults were enrolled into challenge studies in a hospital setting and followed longitudinally; all were exposed to norovirus, half were infected.

Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin.

Iron is critical for life but toxic in excess because of iron-catalysed formation of pro-oxidants that cause tissue damage in a range of disorders. The Nrf2 transcription factor orchestrates cell-intrinsic protective antioxidant responses, and the peptide hormone hepcidin maintains systemic iron homeostasis, but is pathophysiologically decreased in haemochromatosis and beta-thalassaemia. Here, we show that Nrf2 is activated by iron-induced, mitochondria-derived pro-oxidants and drives Bmp6 expression in liver sinusoid endothelial cells, which in turn increases hepcidin synthesis by neighbouring hepatocytes.

Vitamin D, bone mineral density and risk of fracture in people with intellectual disabilities.

Background: People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors.

Method: We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment.

Iron Status and Associated Malaria Risk Among African Children.

Background: It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child's iron status influences their subsequent risk of malaria infection in sub-Saharan Africa.

Methods: We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0-7 years and conducted prospective surveillance for episodes of malaria.

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice.

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients' FGF-21 results were assessed by the use of age-adjusted -scores based on normalised FGF-21 values from a healthy population.

25-Hydroxy- and 1α,25-Dihydroxycholecalciferol Have Greater Potencies than 25-Hydroxy- and 1α,25-Dihydroxyergocalciferol in Modulating Cultured Human and Mouse Osteoblast Activities.

Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts. 50-1000 nM 25(OH) and 0.

The 24-hour normothermic machine perfusion of discarded human liver grafts.

Donor organ shortage necessitates use of less than optimal donor allografts for transplantation. The current cold storage preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation (NMP) of liver allografts.

Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts.

The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D [25(OH)D] (100 or 500 nmolL) and 1,25-dihydroxy vitamin D [1,25(OH)D] (0.

Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia.

Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus.

Point-of-care testing of electrolytes and calcium using blood gas analysers: it is time we trusted the results.

Background: Point-of-care testing allows rapid analysis of samples to facilitate prompt clinical decisions. Electrolyte and calcium abnormalities are common in acutely ill patients and can be associated with life-threatening consequences. There is uncertainty whether clinical decisions can be based on the results obtained from blood gas analysers or if laboratory results should be awaited.

Vitamin D deficiency in patients with intellectual disabilities: prevalence, risk factors and management strategies.

Background: People with intellectual disabilities have a high risk of osteoporosis and fractures, which could partly be as a result of vitamin D deficiency.

Aims: To compare the serum vitamin D (25(OH)D) levels of 155 patients with intellectual disabilities under psychiatric care and 192 controls, investigate potential risk factors for vitamin D deficiency in people with intellectual disabilities and assess available treatments.

Method: Cross-sectional observational study followed by treatment evaluation.

Early change in invasive measures of microvascular function can predict myocardial recovery following PCI for ST-elevation myocardial infarction.

Aims: Predicting the likely success of primary PCI to salvage potential infarcted myocardium is desirable. We compared early invasive parameters of coronary microcirculation function with the levels of circulating endothelin (ET-1) and 6-month ejection fraction after STEMI.

Methods And Results: Forty-four STEMI patients underwent assessment of coronary flow reserve (CFR) and index of myocardial resistance (IMR) on completion of PPCI and one day later.

IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children.

Background: We carried out a technical evaluation of the Immunodiagnostic Systems (IDS) automated intact procollagen-I N-terminus propeptide (PINP) assay on the iSYS platform, and established reference intervals for PINP in both adults and children.

Methods: Assay imprecision, recovery and interference were studied. Serum and plasma values were compared, and PINP stability was assessed.

Methods for the investigation of thyroid function.

In the developed world, all routine clinical laboratories should be able to perform tests for the assessment of the pituitary-thyroid axis. Testing strategies usually involve the measurement of thyroid-stimulating hormone (TSH), either alone or in combination with free thyroxine (FT4), which itself should also be measured when TSH is abnormal or if there is a suspicion of pituitary disease. Based on these findings, clinical history and medications such as amiodarone, free tri-iodothyronine (FT3), thyroid-binding globulin (TBG), and/or autoantibodies may then be measured.

Safety of antipsychotics in people with intellectual disability.

Background: Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.

Aims: To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.

Method: Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.

Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model.

Background: Steatotic livers are increasingly common in the donor population. Cold storage of steatotic livers exacerbates ischemia-reperfuson injury and risks primary nonfunction and recipient death. Normothermic preservation avoids prolonged cooling of the organ and may be well suited to the preservation and resuscitation of damaged livers.

Normothermic perfusion: a new paradigm for organ preservation.

Objective: Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation.